Liquid bromine is used to prepare a variety of brominated compounds through substitution reactions. This includes commercially important products such as i) tetrabromobisphenol-A (TBBPA)—a flame retardant, ii) eosin—a pigment used in personal care products, iii) bromoacetanilide—an analgesic and antipyretic agent, iv) tribromophenol—an intermediate used in the manufacture of antiseptic, germicide, fungicide, fire extinguishing fluids, fire retardant. and v) 2-bromo-4-nitro acetanilide—a drug intermediate used in the preparation of nimenslide. However, liquid bromine is hazardous by nature and requires extreme care in its production, transportation, and utilization. Besides this, special equipments are required to handle liquid bromine. Moreover, for substitution reactions depicted by equation 1, half of the bromine atoms end up in the effluent as hydrobromic acid.R—H+Br2→RBr+HBr  (1)where R=aromatic substrate.
Reference is made to Survey of Organic Syntheses, Published by Wiley-Inter Science, New York, 1970, Chapter 7 by C. A. Buechler and D. E. Pearson who have reported the preparation of tribromophenol by the interaction of phenol with liquid bromine in a liquid phase. In this process more than 50% of bromine atom ends up as hydrobromic acid as byproduct. The main drawback of this method is the use of hazardous and corrosive liquid bromine. Further, it requires special equipments for handling the liquid bromine. The atomic efficiency of liquid bromine is only 50 percent.
U.S. Pat. No. 5,475,153 (1995) to S. Armstrong discloses the preparation of tetrabromobisphenol-A by reacting bisphenol-A with liquid bromine. Here, hydrogen peroxide was used as oxidizing agent to oxidize hydrobromic acid formed as byproduct to liberate bromine which will react with the unreacted bisphenol-A. The main drawback of this process is the use of hazardous and corrosive liquid bromine. Moreover, the addition of oxidizing agent will increase the unit operations as well as the reaction time.
Z. E. Jolles in his book entitled Bromine and its Compounds, Published by Ernest Benn Ltd., London, 1966, p 394 have reported the preparation of 3-bromomethyl-thiophene by adding 2 moles of N-bromosuccinimide to a separately prepared solution of (i) 2.24 moles of 3-methyl-thiophene; (ii) 0.0165 moles of benzoyl peroxide in 700 ml dry benzene and keeping the reaction mixture under stirring at reflux conditions. In this process, prior to recovery of the product by distillation of benzene, the reaction mixture after complete addition of succinimide is cooled below 5° C. The drawback of this process is that the reagent, N-bromosuccinimide is prepared using liquid brimine at temperature below 5° C. in highly alkaline solution. Cooling of reaction mixture below 5° C. also makes the process cost-intensive. Liquid bromine is corrosive and requires special device to handle it. Besides, benzene is carcinogenic and its recovery by distillation makes the process complicated and needs special care.
Brominating agents that are easy to handle are known but are used mainly for more selective transformations or those where bromine is less effective. A. Groweiss in Organic Process & Development 2000, 4, 30-33, discloses the preparation of active brominating species. In this process a strong acid viz. H2SO4 is slowly added to a stirred aqueous solution or slurry of the reagent containing stoichiometric quantity of sodium bromate and deactivating substituents like nitrobenzene; benzoic acid; benzaldehyde, 4-nitrofluorobenzene and 4-fluorobenzoic acid, while maintaining the temperature in the range of 40-100° C. The drawback of this process is that sodium bromate is costly and its use cannot be justified in more conventional bromination reactions that can be affected by liquid bromine as such. Moreover, the use of sulphuric acid and deactivating substituents are more prone to health hazard, at high temperature. Sulphuric acid is also corrosive in nature.
P. C. Merker et al (J. Chem. Ed. 26, 1949 p 613) have disclosed the preparation of p-bromoacetanilide by separately preparing a solution of acetanilide (0.232 moles) in cold glacial acetic acid and reacting this solution with pyridiniumbromideperbromide (0.12 moles) in 40 ml hot glacial acetic acid. The resultant mixture was allowed to stand for 30 minutes at room temperature, and then 2 ml of saturated sodium bisulfite solution was added to aqueous solution. The resulting mass was filtered, washed with water and finally recrystallized from hot 95% aqueous ethanol to yield p-bromoacetanilide. The drawbacks of this method are that the brominating agent requires liquid bromine and hydrobromic acid in its preparation which are corrosive and difficult to handle. (L. F. Fieser and M. Fieser, Reagents for Organic Chemistry Vol. 1, John Wiley, New York, 1967, p967) The reagent is costlier than liquid bromine. It involves multi steps making the process less cost benefit
G. Rothenberg and J. H. Clark in Organic Process & Development 2000, 4, 270-274, have disclosed the catalytic bromination of aromatic compounds using alkali bromide or hydrobromic acid and hydrogen peroxide in the presence of 1-2 mol percent vanadium pentoxide catalyst. The drawbacks of this method are that more than stoichiometric quantities of hydrogen peroxide are required and the reaction needs a catalyst. Such catalytic protocols, in general, have several shortcomings like oxidative instability, high purification cost, strict pH and temperature controls. Besides, these reactions require stoichiometric amounts of metal to ensure satisfactory activity.
U.S. Pat. No. 5,817,888 (1998) to H. Y. Elnagar discloses a bromination process wherein organic compounds were selectively brominated in the para-position in high purity and yield. In this bromination process bromine chloride solution was used as brominating reagent which was slowly added at a controlled rate to a solution of aromatic compound maintained at a temperature around 0-4° C. under stirring. At the closure of the reaction, the reaction was quenched with few drops of saturated sodium sulfite solution and then diluted with normal organic solvents. The disadvantages of this method is that the preparation of brominating reagent, bromine chloride, still requires hazardous liquid bromine and chlorine gas under specified conditions.
Pending Application No. PCT/IB02/00386 dated Jan. 25, 2002 to G. Ramachandraiah et al reports the preparation of non-hazardous brominating reagent suitable for aromatic substitution reactions. In this method, calculated amounts of commercially available 4% hypochlorite solution was added to an industrial alkaline bromine mixture and allowed to stand for 24 h for completion of the desired reaction, optionally followed by evaporation to get brominating reagent in solid form. The drawbacks of this process are that, the volumes of hypochlorite solution required to achieve the desired bromide to bromate ratio, is large which unnecessarily increase the process cost or require large containers to handle bromination reactions. The reaction between bromide and hypochlorite and the subsequent reactions are slow as they are highly pH dependent. Further, the hypochlorite solution contains chlorate ions as an integral part in considerable levels, which being a strong oxidizing agent in acidic solutions, may take part in the bromination reactions and produce unwanted side products deteriorating the quality of the product.